Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency

Homocystinuria caused by cystathionine ß-synthase (CBS) deficiency is an inherited metabolic disorder that affects multiple systems, including the eye, skeletal system, vascular system and central nervous system. Affected individuals lack a particular enzyme called cystathionine ß-synthase, which leads to a buildup of amino acid homocysteine in the body. CBS deficiency causes nearsightedness in infancy, dislocated lenses before age eight years, tall and thin appearance, and abnormal blood clots in veins and arteries known as thromboembolism that typically appear in adolescence. Intelligence of individuals with untreated homocystinuria varies widely, with average at borderline to mild mental disability. Thromboembolism is the major cause of early death and morbidity. Vitamin B6 supplement and diet treatment may control the level of homocysteine in the blood and reduce complications. Homocystinuria due to CBS deficiency is caused by pathogenic variants in the CBS gene. Symptoms and B6-responsiveness can vary depending on the pathogenic variants present in a person.

Homocystinuria caused by CBS deficiency is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for homocystinuria caused by CBS deficiency. However, the risk to have a child affected with homocystinuria caused by CBS deficiency is increased. Testing of reproductive partners is recommended for carriers of homocystinuria caused by CBS deficiency.

Homocystinuria caused by CBS deficiency affects people in all ethnic groups around the world. It is estimated that at least 1 in every 200,000 to 335,000 newborns is affected worldwide. Some countries report a higher rate of affected newborns; in Qatar it is 1 in 1,800, in Norway it is 1 in 6,400, in Germany it is 1 in 17,800, and in Ireland it is 1in 65,000.

Genetics Home Reference: Homocystinuria (http://ghr.nlm.nih.gov/)
Genetic Alliance: Homocystinuria due to CBS deficiency (http://www.diseaseinfosearch.org/)
STAR-G (Screening, Technology and Research in Genetics): Newborn Screening of homocystinuria (http://www.newbornscreening.info/)

OMIM [CBS: 236200](http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing